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Marc Goalstone, Ph.D.

Associate Professor of Medicine


My lab is involved with determining specific parts of insulin signaling as it relates to atherosclerosis and obesity. In particular, we have found that when arterial smooth muscle cells and fat cells become resistant to insulin’s metabolic actions (i.e., utilization of glucose), they become more sensitive to insulin’s mitogenic signals, and in turn become more proliferative and thus increase in number. For smooth muscle cells, they divide and invade the lumen of the artery and block blood flow. For fat cells, they divide and cause increased obesity that can lead to the risk of cardiovascular diseases. We have determined a key enzyme (farnesyltransferase alpha-subunit) in the mitogenic pathway of insulin signaling that when mutated blocks the proliferative action of insulin on vascular smooth muscle cells and fat cells. This suggests that this enzyme could be a target for pharmaceutical therapy, which would block or slow the processes of atherosclerosis and obesity, and thus decrease the chances of cardiovascular diseases.

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  • Dysregulation in insulin

​Selected Publications

  1. Insulin augments tumor necrosis factor-alpha stimulated expression of vascular cell adhesion molecule-1 in vascular endothelial cells.
    Mackesy DZ, Goalstone ML.
    J Inflamm (Lond). 2011 Nov 17;8:34.
     
  2. ERK5: a novel IKKα-kinase in rat hippocampal neurons.
    Goalstone ML.
    Can J Neurol Sci. 2011 Jul;38(4):639-48.
     
  3. Glucose activates prenyltransferases in pancreatic islet beta-cells.
    Goalstone ML, Kamath V, Kowluru A.
    Biochem Biophys Res Commun. 2010 Jan 1;391(1):895-8. Epub 2009 Nov 29.
     
  4. Dominant-negative alpha-subunit of farnesyl- and geranyltransferase inhibits glucose-stimulated, but not KCl-stimulated, insulin secretion in INS 832/13 cells.
    Veluthakal R, Kaur H, Goalstone M, Kowluru A.
    Diabetes. 2007 Jan;56(1):204-10.
     
  5. Regulation of ERK5 by insulin and angiotensin-II in vascular smooth muscle cells.
    Sharma G, Goalstone ML.
    Biochem Biophys Res Commun. 2007 Mar 23;354(4):1078-83. Epub 2007 Jan 26.
     
  6. Dominant negative FTase (DNFTalpha) inhibits ERK5, MEF2C and CREB activation in adipogenesis.
    Sharma G, Goalstone ML.
    Mol Cell Endocrinol. 2005 Dec 21;245(1-2):93-104. Epub 2005 Dec 13.
     
  7. Insulin sensitivity determines the effectiveness of dietary macronutrient composition on weight loss in obese women.
    Cornier MA, Donahoo WT, Pereira R, Gurevich I, Westergren R, Enerback S, Eckel PJ, Goalstone ML, Hill JO, Eckel RH, Draznin B.
    Obes Res. 2005 Apr;13(4):703-9.
     
  8. Molecular mechanisms of insulin resistance that impact cardiovascular biology.
    Wang CC, Goalstone ML, Draznin B.
    Diabetes. 2004 Nov;53(11):2735-40. Review.
     
  9. Garlic extract methylallyl thiosulfinate blocks insulin potentiation of platelet-derived growth factor-stimulated migration of vascular smooth muscle cells.
    Golovchenko I, Yang CH, Goalstone ML, Draznin B.
    Metabolism. 2003 Feb;52(2):254-9.
     
  10. Enhanced insulin signaling via Shc in human breast cancer.
    Finlayson CA, Chappell J, Leitner JW, Goalstone ML, Garrity M, Nawaz S, Ciaraldi TP, Draznin B.
    Metabolism. 2003 Dec;52(12):1606-11.
     
  11. Dominant negative alpha-subunit of farnesyl- and geranylgeranyl-transferase I inhibits insulin-induced differentiation of 3T3-L1 pre-adipocytes.
    Solomon CS, Leitner JW, Goalstone ML.
    Int J Obes Relat Metab Disord. 2003 Jan;27(1):40-7.
     
  12. Dominant negative alpha-subunit of FTase inhibits effects of insulin and IGF-I in MCF-7 cells.
    Solomon CS, Goalstone ML.
    Biochem Biophys Res Commun. 2002 Mar 1;291(3):458-65.
     

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Graduate School
Ph.D., University of Denver, Denver, Colorado (1995)
M.A., University of Colorado at Denver, Denver, Colorado (1992)

Undergraduate School
B.A., The Colorado College, Colorado Springs, Colorado (1974)

Other
Associates degree in Law, Denver Paralegal Institute, Denver, Colorado (1979)


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Daniel MacKesy ​Professional Research Assistant